Onychomycosis is the most common nail disease.
It has been proven that 50% of cases of changes in the nail plates are associated with a fungal infection.Epidemiological studies conducted in Russia and foreign countries have revealed a high incidence of onychomycosis, which varied from 2 to 13% in the general population.The risk of developing onychomycosis is higher in elderly patients.For example, in people over 70 years of age, the prevalence of onychomycosis of the feet can be 50% or higher.It is believed that this is facilitated by the slow growth of nail plates, peripheral and main circulation disorders in the elderly.A high incidence of onychomycosis is also detected in patients with immunodeficiency conditions (including AIDS patients) and in patients with diabetes mellitus.
Often patients and some doctors perceive onychomycosis as an exclusively aesthetic problem.However, this is a serious disease that occurs chronically and in cases of immunodeficiency or decompensation of endocrine diseases can cause the development of widespread mycosis of the skin and its appendages.Onychomycosis is often associated with the development of serious complications, such as diabetic foot, chronic erysipelas of the extremities, lymphostasis and elephantiasis.In patients receiving cytostatic or immunosuppressive therapy, the disease can cause the development of invasive mycoses.This is why the treatment of onychomycosis is necessary and should be carried out at the right time.
Only a few decades ago, the treatment of onychomycosis was labor intensive, long and unpromising.The drugs used for the treatment of fungal diseases of the skin and its appendages were characterized by low effectiveness and high toxicity.To achieve a positive result, long-term treatment or an increase in the dose of drugs was required, which was often accompanied by serious complications.Some treatments were potentially life-threatening to patients.For example, X-ray therapy, the use of thallium and mercury led to the development of skin cancer, diseases of the brain and internal organs in patients.
The appearance of highly effective and low-toxic antifungal drugs has greatly facilitated the treatment of fungal diseases of the skin and its appendages.However, the results of the use of new antifungals were not satisfactory.Controlled clinical trials have shown that the effectiveness of systemic antifungals after treatment is from 40 to 80%, and after 5 years - from 14 to 50%.At the same time, the effectiveness of therapy for onychomycosis increases with the use of complex treatment methods, which include the use of etiotropic drugs and agents that affect pathogenesis.Also, as a result of clinical trials conducted in European countries, it was found that the effectiveness of the treatment of onychomycosis can be increased by an average of 15% with the combined use of systemic antimycotics and antifungal varnish containing amorolfine.
Treatment
For the treatment of onychomycosis, drugs that differ in chemical composition, mechanism of action, pharmacokinetics and spectrum of antifungal activity are used.A common property for them is a specific effect on pathogenic fungi.This group consists of azoles (itraconazole, fluconazole, ketoconazole), allylamines (terbinafine, naftifine), griseofulvin, amorolfine, ciclopirox.For the treatment of onychomycosis, systemic drugs belonging to the azole group - itraconazole, fluconazole, as well as the allylamine group - terbinafine are used.Griseofulvin and ketoconazole are currently not prescribed for the treatment of onychomycosis due to low effectiveness and high risk of side effects.Varnishes and solutions containing amorolfine and ciclopirox are used as external agents for onychomycosis.
Allylamineare synthetic antifungals.Allylamines mainly act on dermatomycetes, while they have a fungicidal effect.The mechanism of their action is to inhibit the enzyme squalene epoxidase, which participates in the synthesis of ergosterol, the main structural component of the cell membrane of dermatomycetes.Allylamines include terbinafine and naftifine.
Allylamines are active against most dermatomycetes (Epidermophyton spp., Trichophyton spp., Microsporum spp., Malassezia spp.), the causative agent of chromomycosis and some other fungi.
Indications for oral administration of terbinafine are onychomycosis, common forms of skin dermatomycosis, scalp mycosis, chromomycosis.Indications for external use of terbinafine and naftifine include limited skin lesions due to mycoses, pityriasis versicolor and cutaneous candidiasis.Terbinafine has high bioavailability and is well absorbed from the gastrointestinal tract, regardless of food intake.In high concentrations, the drug accumulates in the stratum corneum of the skin, nail plates, hair and is secreted with the secretions of sweat and sebaceous glands.Absorption of terbinafine when applied topically is less than 5%, naftifine - 4-6%.The concentration of terbinafine and naftifine in the skin and its appendages significantly exceeds the MIC for the main pathogens of dermatomycosis.Correction of the dosage regimen of terbinafine may be required when it is combined with inducers (rifampicin) or inhibitors of liver microsomal enzymes (cimetidine), since the former increase its clearance, and the latter reduce it.
As a result of numerous multicenter controlled clinical trials, it was found that terbinafine is the most effective antifungal in the treatment of onychomycosis.
Terbinafineused for widespread skin lesions, onychomycosis, chromomycosis, in such cases terbinafine is prescribed orally.Terbinafine is the drug of choice in the treatment of onychomycosis, as it is most effective against the main causative agents of onychomycosis - dermatomycetes.Contraindications for the use of allylamines are allergic reactions to drugs of the allylamine group, pregnancy, breastfeeding, age under 2 years, liver diseases accompanied by impaired liver function (increased transaminases).
azoles- the largest group of synthetic antifungals.In 1984, the first systemic antifungal drug from the azole group, ketoconazole, was introduced in practice, in 1990, fluconazole, and in 1992, itraconazole.
Azoles used as systemic drugs mainly have fungistatic activity.An important advantage of azoles over other drugs is the broad spectrum of their antifungal activity.Itraconazole is active in vitro against most pathogens of onychomycosis - dermatomycetes (Epidermophyton spp., Trichophyton spp., Microsporum spp.), Candida spp.(C. albicans, C. parapsilosis, C. tropicalis, C. lusitaniae, etc.), Aspergillus spp., Fusarium spp., S. Shenckii, etc.Fluconazole is active against dermatomycetes (Epidermophyton spp., Trichophyton spp., and Candida spp.) (C. albicans, C. parapsilosis, C. tropicalis, C. lusitaniae, etc.), but does not affect Aspergillus spp., Scopulariopsis spp., Scedosporium spp.
The pharmacokinetics of different azoles are different.Fluconazole (90%) is well absorbed from the gastrointestinal tract.For good absorption of itraconazole, a normal level of acidity is needed.If a patient taking these drugs has low acidity, their absorption is reduced and, consequently, their bioavailability is reduced.Absorption of itraconazole solution is higher than that of itraconazole capsules.Itraconazole capsules should be taken with food, while Itraconazole solution should be taken on an empty stomach.
Itraconazole is metabolized in the liver and excreted from the body through the gastrointestinal tract.It is also secreted in small amounts by the sebaceous and sweat glands.Fluconazole is partially metabolized and excreted mostly unchanged by the kidneys (80%).
Itraconazole interacts with many medications.The bioavailability of ketoconazole and itraconazole is reduced when taking antacids, anticholinergics, H2 blockers, proton pump inhibitors and didanosine.Itraconazole is an active inhibitor of cytochrome P450 isoenzymes and may alter the metabolism of many drugs.Fluconazole affects the metabolism of drugs to a lesser extent.It is unacceptable to take azoles with terfenadine, astemizole, cisapride, quinidine, as lethal ventricular arrhythmias may develop.The simultaneous use of azoles and oral antidiabetic drugs requires continuous monitoring of blood glucose levels, as hypoglycemia may develop.Taking indirect anticoagulants of the coumarin and azole group may be associated with hypocoagulation and bleeding;therefore, control of hemostasis is necessary.Itraconazole can increase the blood concentration of cyclosporine and digoxin, and fluconazole - theophylline and cause the development of a toxic effect.Dose adjustment and continuous monitoring of blood drug concentrations are required.The combined use of itraconazole with lovastatin, simvastatin, rifampicin, isoniazid, carbamazepine, cimetidine, clarithromycin, erythromycin is contraindicated.Fluconazole should not be used with isoniazid and terfenadine.
Itraconazoleused for dermatomycosis (athlete's foot, trichophytosis, microsporia), pityriasis versicolor, candidiasis of the skin, nails and mucous membranes, esophagus, vulvovaginal candidiasis, cryptococcosis, aspergillosis, pheohyphomycosis, endemicomycosis, mycomycosis, sporromycosis, endemicmycosis in AIDS.
Fluconazoleused for the treatment of generalized candidiasis, all forms of invasive candidiasis, including in immunocompromised patients, genital candidiasis, candidiasis of the skin, its appendages and mucous membranes.Recently, due to safety and good tolerance, fluconazole is increasingly used for the treatment of dermatomycosis patients with damage to the skin and its appendages (nails and hair).
Amorolfineincluded in the varnish used to treat onychomycosis.The mechanism of action of amorolfine is to disrupt the synthesis of ergosterol, the main component of the cell membrane of mushrooms.It has fungistatic and fungicidal effects.It has a wide spectrum of action.The concentration of amorolfine in the nail plate significantly exceeds the MIC for the main pathogens of dermatomycosis for 7 days.Therefore, the drug can be used no more than 1-2 times a week, which makes its use economically profitable.Contraindications: allergic reactions to amorolfine, infancy and young children.Spray as monotherapy is prescribed when no more than 1-3 nail plates are affected and no more than 1/2 of the area from the distal end is affected.Amorolfine can also be used in combination with systemic antifungals for more widespread nail damage.
Ciclopiroxhas a fungistatic effect.Active against dermatomycetes, yeast-like and filamentous fungi, mold, as well as some gram-negative and gram-positive bacteria.Ciclopirox (spray) is used as monotherapy when no more than 1-3 nail plates are affected by no more than 1/2 of the area from the distal end.Ciclopirox can also be used in combination with systemic antifungals for more widespread nail damage.Contraindications: allergic reactions to ciclopirox, infancy and early childhood, pregnancy and lactation.
List of laboratory tests recommended when prescribing systemic antifungal drugs.
- Clinical blood test.
- General analysis of urine.
- Biochemical blood analysis (ALT, AST, bilirubin, creatinine).
- Ultrasound of abdominal organs and kidneys (preferred).
- Pregnancy test (preferred).
Treatment of basic diseases.The effectiveness of the use of antimycotics increases with the correction of pathological conditions that contribute to the development of onychomycosis.Before starting antifungal therapy in patients with somatic, endocrine, neurological diseases and with blood circulation disorders in the extremities, it is necessary to perform an examination to identify the main symptom complex that contributed to the development of dermatomycosis.Thus, the main objectives of pathogenetic therapy are the improvement of microcirculation in the distal parts of the extremities, the venous outflow of the extremities, the normalization of the level of thyroid stimulating hormones in patients with thyroid disease, carbohydrate metabolism in patients with diabetes mellitus, etc.As a result of many years of research, it has been proven that one of the main reasons for the development of dermatomyos disorders.pituitary-hypothalamus-gonadal system.This leads to blood circulation disorders in the distal extremities, microcirculation disorders and peripheral innervation.A group of measures aimed at correcting these disorders include acupuncture, transcranial electrical stimulation of the subcortical centers of the brain and the prescription of drugs that correct the functioning of the sympathetic and parasympathetic autonomic nervous system.All this makes it possible to achieve a faster clinical effect in the treatment of dermatomycosis.It is advisable to prescribe pathogenetic therapy in dermatomycosis patients with underlying diseases before starting etiotropic treatment and to continue it throughout the course of taking antifungal drugs.
Symptomatic therapyof dermatomycosis, aimed at reducing subjective complaints of patients and objective manifestations of the disease, cannot replace etiotropic therapy.However, its use in combination with antifungal drugs makes it possible to quickly improve the condition of patients, reduce the feeling of discomfort and eliminate cosmetic defects.With onychomycosis, the biggest concern for patients is caused by deformed, significantly thickened (hypertrophied) nail plates - onychogryphosis.To correct this condition, a hard pedicure is used.Using a device that resembles a dental turbine, in a short period of time the changed areas of the nails, hyperkeratotic areas, horny masses from the skin and calluses are mechanically removed.In this case, there is no trauma to the nail matrix and the patient remains functional after the procedure.
For limited nail damage (no more than 3 nail plates and no more than 1/2 in the area from the distal edge), topical preparations are used.It is recommended to start the treatment by cleaning the affected area of the nail plate using a hard pedicure or keratolytic agents.Then, antifungal drugs are applied to the affected nail plate.An amorolfine solution containing ciclopirox is applied to the nail plate 1-2 times a week.Before applying the varnish, you do not need to clean the nail plate from the previous layers of the preparation.The varnish is applied daily until the healthy nail plate is fully grown.On the 7th day, the nail plate is cleaned using any cosmetic cleaner for nail polish.There are conflicting reports in the literature regarding the effectiveness of this treatment method.The percentage of recovery for patients is shown from 5-9 to 50%.
In case of extensive damage to the nail plates on the fingers, a complex of treatment measures should include the prescription of a systemic antimycotic, nail cleaning and external therapy with antifungal drugs.To prevent re-infection, it is necessary to treat the patient's gloves and disinfect personal hygiene items (towels, towels, nail files, razors and scrapers for the treatment of skin and nails).
The drug of choice for the treatment of onychomycosis of any location is terbinafine.It is prescribed to adults and children weighing more than 10 kg, 250 mg per day for 6 weeks.Children over 2 years weighing less than 20 kg are prescribed terbinafine at the rate of 67.5 mg/kg per day, from 20 to 40 kg - 125 mg/kg per day for 6 weeks.Back-up drugs are products containing itraconazole and fluconazole.Itraconazole is used in two regimens: 200 mg per day for 3 months or 200 mg twice per day for 7 days in the first and fifth weeks from the start of therapy.Itraconazole is not prescribed for the treatment of onychomycosis in children.Fluconazole is recommended to be taken 150 mg once a week for 3-6 months.
Carrying out complex therapy, consisting of taking a systemic antimycotic, cleaning the nails, local use of antifungal drugs, as well as anti-epidemiological measures, ensures high efficiency in the treatment of onychomycosis of the feet.Terbinafine is prescribed to adults and children weighing more than 10 kg, 250 mg per day for 12 weeks or more.For children over 2 years weighing less than 20 kg, the drug is prescribed at the rate of 67.5 mg/kg per day, from 20 to 40 kg - 125 mg/kg per day for 12 weeks.Fluconazole is recommended to be used in a dose of 150-300 mg once a week for 6-12 months.Itraconazole is used in two regimens: 200 mg daily for 3 months or 200 mg twice daily for 7 days in the first, fifth, and ninth weeks.If the big toes are affected, it is recommended to carry out the 4th course of pulse therapy in the thirteenth week from the beginning of the therapy.Itraconazole is not used to treat onychomycosis in children.
The criteria for the mycological cure of onychomycosis are the negative results of the microscopic and cultural examination of the nail plate.After treatment with itraconazole and terbinafine, healthy nail plates do not grow completely, so complete clinical recovery can be observed only 2-4 months after the end of taking antifungal drugs.